Prediction of the interacting surfaces in a trimolecular complex formed between the major dust mite allergen Der p 1, a mouse monoclonal anti-Der p 1antibody, and its anti-idiotype

Background-Two mouse monoclonal antibodies (mAbs) have been described recen tly; namely, rnAb 2C7 (IgC2b kappa), which is directed against the major ho use dust mite allergen Der p 1, and mAb 2G10 (IgG1 kappa), which is an anti -idiotypic antibody raised against mAb 2C7. The antiidiotype mAb 2G10 does not block the binding of mAb 2C7 to Der p 1, which means that mAb 2C7 can s imultaneously bind to Der p 1 and to mAb 2G10, thereby generating a trimole cular complex consisting of antigen-idiotype-anti-idiotype. Aim-To sequence and model the V region of the anti-idiotypic antibody mAb 2 G10 to enable the prediction of the interacting surfaces in the trimolecula r complex consisting of Der p 1-mAb 2C7-mAb 2G10. Methods-DNA sequencing of mAb 2G10 was carried out and the Swiss Model and Swiss PDB-Viewer programs were used to build a three dimensional model of t he trimolecular complex. Results-Complementarity of shape and charge was revealed when comparing the protrusion of the previously determined Der p 1 epitope (Leu147-Gln160) wi th the cavity formed by the complementarity determining regions (CDRs) of m Ab 2C7. Such complementarity was also observed between the rnAb 2C7 epitope predicted to be recognised by mAb 2G10 (residues Lys19 from framework regi on 1 (FRW1) and Ser74-Gln81 from FRW3) and residues from the CDRs of mAb 2G 10 (a negatively charged patch flanked by the residues Asp55H/Glu58H and Gl u27L/Glu27cL). As expected, the location of the mAb 2C7 epitope recognised by mAb 2G10 does not appear to interfere with the binding of Der p 1 to mAb 2C7. Conclusion-Although the results obtained represent only an approximation, t hey nevertheless provide a rare insight into how an antigen (Der p 1) might bind to its antibody (mAb 2C7) while in complex with an anti-idiotype (mAb 2G10).